title: Molecular, genetic, and functional analysis of homozygous C8 beta-chain deficiency in two siblings.
abstract: C8 deficiency is associated with an increased susceptibility to neisserial infections. We present a case of an 11 year old boy who suffered from infection with Neisseria meningitidis. Medical history of the patient and his family (n = 5) did not indicate any previous immunodeficiency symptoms. Results from the analysis of phagocyte and lymphocyte functions were within the normal range. No hemolytic activities of the classical (CH50) and the alternative (APH50) pathways of complement were measurable, and SC5b-9 protein complexes could not be detected in the patient's plasma. Further analysis by highly sensitive ELISA and functional assays revealed a complete deficiency of C8. Upon the reconstitution with purified C8 total hemolytic activity could be restored. SDS-PAGE and Western blot analysis established a deficiency of the C8 beta chain. Genetic analysis at the genomic DNA level demonstrated the common C-T mutation in exon 9 of the C8B gene. Family analysis presented the older sister with non-detectable function of C8 in serum, both parents with about half-normal C8 titres, and the younger sister with normal C8 function. The parents and both sisters were asymptomatic, although the older of the sisters presented with the same complete C8 beta-chain deficiency as the patient described.
  
  
  CONCLUSIONS
  the common C-T mutation in the C8B genes is the genetic basis of C8 beta-chain deficiency in two members of this Bosnian family.
authors.affiliation: Institute of Microbiology and Immunology, University of Ljubljana, Slovenia. vkotnik@ibmi.mf.uni-lj.si
authors.forename: V
authors.initials: V
authors.lastname: Kotnik
authors.forename: T
authors.initials: T
authors.lastname: Luznik-Bufon
authors.forename: P M
authors.initials: PM
authors.lastname: Schneider
authors.forename: M
authors.initials: M
authors.lastname: Kirschfink
mesh_terms: D000483:Alleles; D017522:Bosnia and Herzegovina; D002648:Child; D003185:Complement C8 / Q000172:deficiency* / Q000235:genetics* / Q000276:immunology; D015941:Complement Hemolytic Activity Assay; D015938:Complement Membrane Attack Complex / Q000235:genetics / Q000276:immunology; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D005091:Exons; D005260:Female; D006720:Homozygote; D006801:Humans; D008297:Male; D008585:Meningitis, Meningococcal / Q000235:genetics / Q000276:immunology*; D010586:Phagocytes / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D003185:Complement C8; D015938:Complement Membrane Attack Complex; D004247:DNA